SJL/J lymphomas can be used as a model to study the mechanism of MHC expression in normal and malignant cells. Furthermore, the role of variation in MHC expression can be examined for their relationship to tumorigenesis. By using molecular genetic techniques, we will identify, produce and sequence specific cDNA probes for the Ks, Is, and Ds region genes of the SJL/J H-2s complex. Hybridization and sequence analyses will allow the comparison of genomic DNA from normal SJL/J tissue with DNA of Ds-positive and Ds-negative SJL/J lymphomas. We will determine if variations in the RNA are being produced in the Ds-positive and Ds-negative transplantable lymphomas through hybridization analyses. These studies will indicate if regulation of expression of the three Ds gene products occurs at the RNA level. Changes in post-translational processingof the H-2 antigens will be examined using tunicamycin, endoglycosylases and cell-free synthesis techniques. By studying at least 20 Ds-positive and Ds-negative transplantable lymphoma lines, we will determine the various mechanisms for modification of cell surface antigens during tumorigenesis. The association of MHC antigens with the biological properties of these lymphomas will be studied by transforming an aggressive Ds-negative tumor to a Ds-positive tumor using several different approaches (i.e., CaPO4-mediated DNA transfer, protoplast fusion, cell injection). Also, we will use these same methods to examine the role of Ia density in tumorigenesis. Thus, the long-term goal of these genetic investigations is to identify the various controlling mechanisms of MHC expression in normal and malignant cells.